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  • Author or Editor: Richard Ducatelle x
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Abstract

Objective—To determine the prognostic importance of the DNA content and nuclear morphometric variables in melanocytic tumors of cats and dogs.

Sample Population—27 melanocytic tumors of dogs and cats.

Procedures—Biopsy specimens were investigated by quantitative image analysis after the Feulgen staining method. The DNA content (index), nuclear diameter, ploidy balance, proliferation index, hyperploidy, and growth fraction (Ki67) were measured. Using 1- way ANOVA and a Pearson correlation test, the relationships between the different variables were tested. Their role in the prognosis in affected dogs and cats was estimated using the Cox regression test with respect to 6 months postoperative survival rate.

Results—Significant correlations were found between DNA index and ploidy balance and proliferation index. A significant correlation was also found between hyperploidy and DNA index, and between ploidy balance and proliferation index. Significant differences were found between histologically malignant and benign melanocytic tumors but not between primary malignant tumors and metastatic malignant tumors for DNA index and ploidy balance. No correlation was found between DNA variables and survival time.

Conclusion and Clinical Relevance—In melanocytic tumors of cats and dogs, DNA index and ploidy balance can be used to differentiate histologically benign from malignant tumors. However, DNA content and nuclear morphometric variables have little value in predicting survival time. The DNA index and ploidy balance provide an additional tool to evaluate melanocytic tumors of cats and dogs. Survival in dogs and cats with melanocytic tumors, however, is not determined by modifications of DNA content or changes in nuclear morphometry of tumor cells. (Am J Vet Res 2000;61:1074–1079)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate the impact of modulation of the membrane-bound efflux pump P-glycoprotein (P-gp) on plasma concentrations of orally administered prednisolone in dogs.

Animals—7 healthy adult Beagles.

Procedures—Each dog received 3 treatments (control [no treatment], rifampicin [100 mg/d, PO, for 21 days, as an inducer of P-gp], and ketoconazole [100 mg/d, PO, for 21 days, as an inhibitor of P-gp]). A single dose of prednisolone (1 mg/kg, PO) was administered on day 8 of each treatment period. There was a 7-day washout period between subsequent treatments. Plasma concentrations of prednisolone were determined by use of a validated liquid chromatography–tandem mass spectrometry method. Duodenum and colon biopsy specimens were obtained endoscopically from anesthetized dogs and assessed for P-gp protein labeling via immunohistochemical analysis and mRNA quantification via real-time PCR assay. Total fecal collection was performed for evaluation of effects of P-gp modulation on digestion of nutrients.

Results—Rifampicin treatment upregulated duodenal P-gp in dogs and significantly reduced the area under the plasma concentration-time curve of prednisolone. Ketoconazole typically downregulated expression of duodenal P-gp, with a subsequent increase in the area under the plasma concentration-time curve of prednisolone. There was a noticeable interindividual difference in response. Digestion of nutrients was not affected.

Conclusions and Clinical Relevance—Modulation of P-gp expression influenced plasma concentrations of prednisolone after oral administration in dogs. Thus, treatment response to prednisolone may be influenced by coadministration of P-gp–modulating medications or feed ingredients.

Full access
in American Journal of Veterinary Research